Journal of the American Academy of Dermatology Volume 10 issue 5 1984 [doi 10.1016%2FS0190 9622%2884%2970090 9] Schreiber, Michael M.; Moon, Thomas E.; Bozzo, Paul D. Chronic solar ultra

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Chronic solar ultraviolet damage associated 
with malignant melanoma of the skin 
Michael M. Schreiber, M.D.,* Thomas E. Moon, Ph.D., and 
Paul D. Bozzo, M.D.* Tucson, AZ 
A retrospective study of 226 cases of cutaneous malignant melanoma (CMM) 
was done to determine if patients with CMM showed evidence of chronic 
solar ultraviolet radiation damage, i.e., a past history of actinic keratosis 
(AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC) anywhere 
on the patient's skin, and solar elastosis (SE) at the site of a CMM. This 
statistical analysis consisted of 119 clinical records and 158 pathology slides 
after all cases of lentigo CMM were deleted. CMM showed no statistical 
correlation with AK, BCC, SCC, or SE. This supports the idea that it is not 
the chronic solar-ultraviolet radiation exposure that causes CMM. (J AM 
ACAD DERMATOL 10:755-759, 1984.) 
A retrospective study of 226 cases of cutaneous 
malignant melanoma (CMM) was done to deter- 
mine if patients with CMM show evidence of 
chronic solar ultraviolet radiation (UVR) damage, 
i .e. , a past history of actinic keratoses (AK), basal 
cell carcinoma (BCC), squamous cell carcinoma 
(SCC) anywhere on the patient's skin, and solar 
elastosis (SE) at the site of a CMM. The presence 
of these conditions would support the contention 
that chronic solar UVR plays a role in the patho- 
genesis of CMM. 
METHOD 
The 226 available clinical records and 182 available 
histopathology slides of the 533 CMM patients reported 
in our 1981 ~ study were reviewed. Previous histories of 
AK (118 patients), BCC (119 patients), and SCC (123 
patients) were tabulated, as well as the patients' sex, 
age, and CMM location (one patient had metastatic 
CMM and was deleted from the latter part of the analy- 
From the Cancer Center, University of Arizona Health Sciences 
Center (T. E. M.). 
Accepted for publication Sept. 21, 1983. 
Reprint requests to: Dr. Michael M. Schreiber, Associated Der- 
matologists, P.C., 5402 E. Gr;mt Rd., Bldg. F, Tucson, AZ 
85712. 
*Private practice, 
sis). The original 182 CMM histopathology slides were 
studied for the presence of SE coded minimal (none or 
barely seen, i.e., elastic fibers thickened and increased 
in number) (131 patients) and extensive (moderate or 
marked--basophilic degeneration of collagen shown as 
amorphous bundles of basophilic granular material) (51 
patients). 
We found that twenty-seven patients had a diagnosis 
of lentigo maligna melanoma (LMM). All were from 
sun-exposed sites and had SE. Since LMM represents a 
different entity clinically, morphologically, and prog- 
nostically than other types of CMM, patients with a 
diagnosis of LMM were excluded from further analy- 
sis. Thus, 119 clinical records and 158 available 
pathology slides were included in the report. This de- 
creased our numbers of patients with AK (97), BCC 
(99), and SCC (102) from that stated above. 
Statistical tests of association (bivariate and mul- 
tivariate) were carried out using categorical data analy- 
sis methods. If p > 0.1, there was association; if be- 
tween 0.1 and 0.05, then suggestive; if less than 0.05, a 
significant association. 
RESULTS 
The distribution of patient characteristics (sex, 
age, and location), degree of SE, as well as a 
cross-classification of each of these factors are 
shown in Table l, Forty-six percent of the patients 
755 
756 Schreiber et al 
Journal of the 
American Academy of 
Dermatology 
Abbreviations used 
AK actinic keratosis 
BCC basal cell carcinoma 
CMM cutaneous malignant melanoma 
HNAH head, neck, arm, hand 
LF legs, feet 
LMM lentigo maligna melanoma 
SCC squamous cell carcinoma 
SE solar elastosis 
TB trunk, buttock 
UVR ultraviolet radiation 
were male. Their age distribution indicated that 
39% were <50 years of age, while 37% were 
_>60. Also, 42% of the patients had their CMM 
located on the head, neck, arm, or hand area 
(HNAH). Patient sex and CMM location are sig- 
nificantly associated (p = 0.006). Male patients 
had a slightly higher frequency of HNAH (45%) 
as contrasted to female patients (39%). However, 
there was a marked difference in distribution by 
sex for trunk location (male, 47%, versus female, 
29%) and for leg and foot melanoma locations 
(male, 8%, versus female, 32%). Patient age was 
also associated with CMM location (p = 0.004), 
older patients having a higher frequency on the 
HNAH while younger patients had a higher fre- 
quency of trunk melanoma, with approximately 
the same frequency of leg or foot melanoma. Pa- 
tient sex is not associated with patient's age 
(p = 0,31). 
The distribution of the extent of SE is shown in 
Table II. Only 23% (36/158) of patients with 
pathology slides available had extensive SE ap- 
parent. While patient sex was not associated with 
SE (p = 1.00), extent of SE was significantly as- 
sociated with patient age (p = 0.001), with older 
patients having over twice the occurrence of ex- 
tensive SE as compared to younger patients. In 
addition, the extent of SE was also significantly 
associated with locations of CMM (p < 0.0001); 
44% of patients with CMM located on the HNAH 
had extensive SE, contrasted to only 2% of pa- 
tients with CMM located on the trunk and 13% of 
patients with CMM on the leg or foot. 
The association of AK with patient characteris- 
tics is shown in Table II. Forty-seven percent of 
the 119 patients with available information had 
documented prior AK. Patient age was sig- 
nificantly associated with the occurrence of AK, 
with older patients (69%) having a higher fre- 
quency as contrasted to younger patients (34%, 
p = 0.001). Although AK was reported in 56% of 
male and 38% of female patients, this trend was 
not significantly different (p = 0.106). CMM lo- 
cation was not associated with occurrence of AK 
(p = 0.23). 
SE had a highly significant association with 
prior AK (p = 0.009). Of the thirty-six patients 
with no prior AK, 8% had extensive SE while 
33% of the thirty-six patients with prior AK had 
extensive SE. In addition, a significant association 
between AK and SE is not in any way changed 
when other patient characteristics are simulta- 
neously considered using multivariate statistical 
analysis (p = 0.01). Finally, the column with the 
heading (SE/AK) indicates that there was not a 
disproportionate number of patients with infor- 
mation on the prior AK history that also had a 
pathology slide available for review of their extent 
of SE. 
Table II shows the association of prior BCC 
with patient characteristics. Ninety-nine patients 
were avaiIable for inclusion in this table. Thirty- 
four percent (34/99) had a prior history of BCC. 
Age was significantly associated with BCC, older 
patients having a higher frequency (58%) than 
younger patients (21%, p < 0.001). Prior BCC is 
also associated with patient sex, male patients hav- 
ing a higher frequency (46%) than female patients 
(21%, p = 0.01). CMM location was not associ- 
ated with prior BCC (p = 0.52). 
SE was significantly associated with prior BCC 
(p = 0.02). Fourteen percent (6/44) of the patients 
without a prior history of BCC had extensive SE 
as contrasted to 33% (10/34) of patients with a 
history of prior BCC. This association persisted 
even after other patient characteristics were simul- 
taneously considered (p = 0.04). 
The association of SCC with patient charac- 
teristics is shown in Table II. Information was 
available for 102 patients, of whom eighteen had a 
history of prior SCC. Neither patient age, sex, or 
Volume I0 
Number 5, Part 1 
May, 1984 
Chronic solar damage associated with malignant melanoma 757 
Tab le I. Melanoma patient characteristics* 
I Male (%) Female (%) ]_ .<60yr (%) [ >60yr (%) 
Male 61 (48) 31 (42) HNAH 
Female 65 (52) 42 (58) TBLFLF 
Total 126 (100) 73 (100) Total 
(Sex/Age: NA p = 0.306) 
41 (45) 42 (39) 46 (37) 37 (51) 
44 (47) 31 (29) 55 (44) 20 (27) 
7 (8) 34 (32) 25 (20) 16 (22) 
92 (100) 107 (100) 126 (101) 73 (100) 
(Loc/Sex: A p = 0,006) (Loe/Age: A p = 0.004) 
A: Associated; Loc: location; NA: not associated. 
*See abbreviations table at beginning of article for abbreviations not listed. 
Tab le 1I. Association of melanoma patients with history of SE, AK, BCC, SCC with patient 
characteristics and SE* 
SE (%) 
min ext 
Present 36 (23) 46 (47) 
None 122 (77) 51 (53) 
Total 158 97 
Male 56 16 (22) 28/50 (56) 
Female 66 20 (23) 
(SE/Sex: NAp = 1) 
<60 yr 82 13 (14) 
HNAH 
TB 
LF 
SE + AK (%) SE + BCC (%) SE + SCC (%) 
34 (34) 18 (20) 
65 (66) 84 (80) 
99 102 
24/52 (46) 11/51 (22) 
18/47 (38) 10/47 (21) 7/51 (14) 
(AK/Sex: NAp = 0,106) (BCC/Sex: A p = 0.01) (SCC/Sex: NAp = 0.32) 
21/61 (34) 13/63 (21) 8/63 (13) 
SE ext 
>60 yr 40 13 (37) 25/36 (69) 21/36 (58) 10/39 (26) 
(SE/Age: A p = 0.001) (AK/Age: A p = 0.001) (BCC/Age: A p < 0.001) (SCC/Age: NAp = 0.116) 
40 31 (44) 25/46 (54) I8/47 (38) 9/48 (19) 
55 l (2) 14/34 (41) 12/35 (34) 5/34 (15) 
27 4 (13) 7/14 (41) 4/17 (24) 4/20 (20) 
(SE/Loc: A p < 0.0001)(AK/Loc: NAp = 0.23) (BCC/Loc: NAp = 0.52) (SCC/Loc: NAp = 0.583) 
12/36 (46) 10/30 (33) 5/18 (28) 
tot = 72 tot = 74 tot = 77 
(AK/SE: A p = 0.009) (BCC/SE: A p = 0.02) (SCC/SE: NA p = 0.53) 
Multivariate analysis AK/SE: A p = 0.01 BCC/SE: A p = 0.037 SCC/SE: NA p = 0.41 
A: Associated; ext: large amorphous bundles basophilic collagen; Loc: location; min: no elastic fibers/incr, number thick fibers; NA: not 
associated. 
*See abbreviations table at beginning of article for abbreviations not listed. 
location of melanoma was associated with prior 
history of SCC (all p values >-0.12). 
Prior SCC was not significantly associated with 
SE (p = 0.53). This lack of association persisted 
even after the multivariate analysis was carried out 
adjusting for the effects of other patient charac- 
teristics (p = 0.41). 
Table III focuses on patients only with CMM 
located on the HNAH. Forty-nine percent of the 
patients were male and 45% were over the age of 
60. As previously reported during our discussion 
of Table II, 44% of patients with HNAH CMM 
had extensive SE. While patient sex was not as- 
sociated with SE (p = 0.45), patient age was sig- 
nificantly associated with SE (p = 0.004). 
Table III shows the association of AK with pa- 
tient characteristics. Fifty-four percent (25/46) of 
patients included in this table had a prior history of 
AK. There continues to be a significant associa- 
tion between patient age and occurrence of AK 
(p = 0.001). Also, patient sex continues not to be 
associated with AK (p = 0.39). In addition, there 
758 Schreiber et al 
Journal of the 
American Academy of 
Dermatology 
Table HI. Association of HNAH melanoma patients with history of SE, AK, BCC, SCC with 
patient characteristics and SE* 
sE (%) 
min ext SE + AK (%) 
Present -- 31 (44) 25 (46) 18 (38) 9 (19) 
None 40 (56) -- 21 (54) 29 (62) 39 (81) 
Total 71 46 47 48 
Male 17 16 (48) 15/24 (63) 13/25 (52) 5/25 (20) 
Female 23 15 (38) 10/22 (45) 5/22 (23) 4/23 (17) 
(SE/Sex: NAp = 0.365) (AK/Sex: NAp = 0.39) (BCC/Sex: B p = 0.07) (SCC/Sex: NAp = 1) 
<60 yr 28 11 (28) 10/27 (37) 6/28 (21) 3/28 (11) 
>60 yr 12 20 (63) 15/19 (79) 12/19 (63) 6/20 (30) 
(SE/Age: A p = 0.004) (AK/Age: A p -- 0.001) (BCC/Age: A p = 0.009) (SCC/Age: NAp = 0.152) 
12/20 (60) 10/16 (63) 4/9 (64) 
tot = 39 tot = 40 tOt = 41 
(AK/SE: A p = 0.009) (BCC/SE: A p = 0.008) (SCC/SE: NA p = 1) 
SE ext 
Multivariate analysis 
SE + BCC (%) SE + SCC (%) 
A: Associated; B: borderline; ext: large amorphous bundles basophilic collagen; rain: no elastic fibers/incr, number thick fibers; NA: not 
associated. 
*See abbreviations table at beginning of article for abbreviations not listed. 
continues to be a highly significant association be- 
tween history of AK and extent of SE (p = 0.009). 
Note that 60% (12/20) of the HNAH patients with 
a history of AK had extensive SE. 
The association of BCC with patient charac- 
teristics for this selected population is shown in 
Table III. Similar distributions (as compared to 
Table II) are obtained for BCC distribution, with 
38% of patients having a history of prior BCC. 
There was a significant association between pa- 
tient age and history of BCC (p = 0.004), as well 
as an association between patient sex and history 
of BCC (p = 0.04). The association of history of 
BCC with patient age as well as with patient sex is 
similar, as observed in Table II. A higher fre- 
quency was seen in male patients, as well as in 
those over 60 years of age. Also, there continues 
to be a significant association between history of 
BCC and extent of SE (p = 0.008). Note that 63% 
of patients with a history of BCC also had exten- 
sive SE. 
Table III shows the association of SCC with 
patient characteristics. As before (see Table II), 
there are similar distributions for extent of SCC, 
with 19% of patients having a documented SCC. 
Also consistent, history of SCC was not associated 
with patient age (p = 0.15) and not associated 
with patient sex (p = 0.10). In addition, history of 
SCC was not associated with SE (p --- 1.00). 
DISCUSSION 
There is presumptive evidence that chronic 
solar UVR is a carcinogen or co-carcinogen in the 
etiology of CMM. This is supported by the follow- 
ing: (1) increased incidence of CMM in areas 
closer to the equator1; (2) CMM patients usually 
have a history of painful sunburning; (3) CMM 
patients have a poor tanning ability ~'3 and inci- 
dence of CMM is inversely related to degree of 
skin pigmentation; (4) CMM rarely occurs on in- 
frequently sun-exposed sites (breast, genitalia); 
(5) increased incidence of CMM in recent de- 
cades, probably because of more leisure time 
spent in the sun and change in dress; (6) CMM 
occurs at a very young age in patients with 
xeroderma pigmentosum who lack the ability to 
repair UVR-induced deoxyribonucleic acid (DNA) 
damage; (7) increased incidence of CMM follow- 
ing periods of maximum sunspot activity4'5; (8) 
UVB radiation enhances melanocyte mitoses6; (9) 
increased incidence of CMM in summer monthsT; 
(10) susceptible people living in sunny climates all 
of their lives have a higher incidence of CMM 
than people recently moved to the area. s 
Volume 10 
Number 5, Part I 
May, 1984 
Chronic solar damage associated with malignant melanoma 759 
Data not supporting chronic solar UVR as a 
casual agent in CMM production are: (1) less than 
25% of CMM occur on the head and neck (areas of 
chronic sun exposure) whereas 90% of non- 
melanoma skin cancers occur in these areas; (2) a 
high incidence on the back, a nonhabitually sun- 
exposed area; (3) occurrence of CMMon the trunk 
and extremities at younger ages; (4) a large num- 
ber of CMM occur in office workers as compared 
to outdoor workers. 9-11 
It is an accepted idea that most all non- 
melanoma skin cancers (SCC, BCC) are caused by 
solar UVR. They occur most commonly on sun- 
exposed sites and in the older population. These 
habitually sun-exposed sites show a marked in- 
crease in elastic fibers leading to SE, the earliest 
indicator of actinic damage.12,1~ For these reasons, 
we used the presence of SE, BCC, SCC, and AK 
as indicators of chronic actinic damage to the skin. 
The patient distributions and associations ob- 
served in Tables I and II for all patients included in 
this analysis are very similar to the distributions 
and associations observed in Table III that include 
only those patients with CMM located on the 
HNAH areas. This further implies that the location 
of the patient's CMM does not influence the asso- 
ciationof SE with other patients' characteristics 
and the association of SE with patient's prior his- 
tory of AK or skin cancer. 
The associations of SE with age and Iocation, of 
AK with age and SE, of BCC with age, sex, and 
SE are all as expected because AK, SE, and BCC 
are the result of chronic UVR damage. It was 
surprising that a prior history of SCC showed no 
statistical association with age, location, or SE; 
this may be in part due to the small number of 
patients with SCC found in this study. 
In conclusion, we feel that UVR plays some 
role in the production of CMM, but the relation- 
ship is certainly not clear. Perhaps, as suggested, 
the frequency of CMM has a relationship to the 
number of melanocytes at the site of occurrence, 14 
and the sites of chronic sun exposure are protected 
by the tanned and thickened skin. Possibly it is the 
short, occasional, intense exposure to solar UVR 
on untanned skin that triggers the majority of 
CMM. However, the precise role of solar UVR in 
the pathogenesis of CMM is still unknown. 
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